Age of onset and intrinsic neural timescales in first‐episode schizophrenia

Aim To investigate abnormal patterns of intrinsic neural timescales (INT) in first‐episode schizophrenia across different ages of onset, with a focus on differences in neural temporal‐dynamic characteristics between early‐onset and adult‐onset patients. Methods We collected resting‐state fMRI data from 231 first‐episode schizophrenia patients (early‐onset, n = 122; adult‐onset, n = 109) and 153 healthy controls (younger controls, n = 61; older controls, n = 92). INT was computed from the autocorrelation function of the fMRI signal. A two‐way ANOVA tested the Diagnosis × Age‐of‐onset interaction. Further analyses included between‐group comparisons, correlation analyses, and imaging transcriptomic analysis. Results Fourteen region of interests (ROIs) showed significant interaction effects ( P < 0.05/264), predominantly located within the default mode network (DMN, 9 ROIs), with additional involvement of sensorimotor, frontoparietal, memory retrieval, and dorsal attention networks. Group comparisons indicated that early‐onset patients exhibited more widespread INT reductions across multiple regions relative to age‐matched controls, whereas INT abnormalities in adult‐onset patients were more restricted and primarily centered on the DMN. Interaction effects on INT were possibly associated with gene enrichment related to chemical synaptic transmission, glutamatergic signaling, and calcium/calmodulin‐dependent kinase activity. Conclusion INT abnormalities in first‐episode schizophrenia are dependent on age of onset: the early‐onset subtype shows widespread shortening of timescales across multiple brain networks, suggesting broad neurodevelopmental compromise, whereas the adult‐onset subtype exhibits more focal abnormalities centered on the DMN. These findings suggested that INT may serve as a potential neuroimaging biomarker for distinguishing onset‐age subtypes, aiding precise stratification and mechanistic studies of schizophrenia.